Selective CDK7 inhibition with BS-181 suppresses cell proliferation and induces cell cycle arrest and apoptosis in gastric cancer

Autor: Jun Cao, Zhisu Liu, Bo-Yong Wang, Jiwei Chen, Quanyan Liu
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Cell cycle checkpoint
Pharmaceutical Science
Apoptosis
Bioinformatics
Mice
0302 clinical medicine
Drug Discovery
Tumor Cells
Cultured
Medicine
Original Research
Mice
Inbred BALB C
selective CDK7 inhibitor
biology
Kinase
BS-181
Cyclin-Dependent Kinases
XIAP
anticancer activities
030220 oncology & carcinogenesis
Cell Survival
Mice
Nude
Antineoplastic Agents
Structure-Activity Relationship
03 medical and health sciences
Cyclin D1
Stomach Neoplasms
Cyclin-dependent kinase
Animals
Humans
Protein Kinase Inhibitors
Cell Proliferation
Pharmacology
Drug Design
Development and Therapy
Dose-Response Relationship
Drug
business.industry
Cell growth
gastric cancer
Cell Cycle Checkpoints
Neoplasms
Experimental
Pyrimidines
030104 developmental biology
Cell culture
Cancer research
biology.protein
Pyrazoles
Drug Screening Assays
Antitumor
business
Cyclin-Dependent Kinase-Activating Kinase
Zdroj: Drug Design, Development and Therapy
ISSN: 1177-8881
DOI: 10.2147/dddt.s86317
Popis: Bo-Yong Wang, Quan-Yan Liu, Jun Cao, Ji-Wei Chen, Zhi-Su Liu Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China Abstract: Cyclin-dependent kinase (CDK) family members have been considered as attractive therapeutic targets for cancer. In this study, we aim to investigate the anticancer effects of a selective CDK7 inhibitor, BS-181, in gastric cancer (GC) cell line. Human GC cells (BGC823) were cultured with or without BS-181 at different concentrations for 24–72hours. BS-181 significantly reduced the activity of CDK7 with downregulation of cyclin D1 and XIAP in GC cells. Treatment with BS-181 induced cell cycle arrest and apoptosis. The expression of Bax and caspase-3 was significantly increased, while Bcl-2 expression was decreased in cells treated with BS-181. In addition, the inhibition of CDK7 with BS-181 resulted in reduced rates of proliferation, migration, and invasion of gastric cells. Those results demonstrated the anticancer activities of selective CDK7 inhibitor BS-181 in BGC823 cells, suggesting that CDK7 may serve as a novel therapeutic target or the treatment of GC. Keywords: selective CDK7 inhibitor, gastric cancer, BS-181, anticancer activities
Databáze: OpenAIRE
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